General thermodynamic analysis of the dissolution of non-polar molecules into water. Origin of hydrophobicity

Abstract

The Gibbs energy, enthalpy, entropy and heat capacity of transfer from the pure non-polar liquid into water are analysed in detail. It is found that if the combinatorial contribution to the Gibbs energy and entropy of transfer is subtracted from the experimental values, all non-polar solutes in water behave in a universal manner, i.e. all of their thermodynamic transfer functions can be studied with their molecular surface area as the only parameter. This is illustrated with the alkylbenzene series, for which experimental Gibbs energies of transfer in a wide temperature range have been obtained recently. A new interpretation scheme for the thermodynamic transfer functions is presented and contrasted with that due to Privalov and Gill. It is considered that water molecules around the solute undergo a relaxation process which lowers the Gibbs energy, enthalpy and entropy of the system and is responsible for the large heat capacity of transfer. This relaxation process is described here using a two-state model for water molecules obtained from first principles. The negative relaxation contribution to the Gibbs energy promotes solubility, but is overcome by a large positive contribution arising from the creation of a cavity in water and the large differences between solute–solute, water–water and solute–water interactions. The origin of hydrophobicity lies then in the high cohesive energy of water. The proposed interpretation scheme is used to (a) predict the solubility of alkanes in water, (b) understand the origin of the solubility minimum appearing in aqueous solutions of non-polar solutes, (c) rationalize the experimental finding that the enthalpy of transfer becomes zero in a narrow temperature range for many non-polar solutes, (d) discuss the significance of entropy of transfer vs. heat capacity of transfer plots often used to understand the nature of the hydrophobicity of non-polar solutes and proteins, and (e) account for the expected change in sign (with temperature) of the water proton NMR chemical shifts discussed earlier in the literature.